Evidence map›Paper›PMID 39016594›Full record

Trial reportAntimicrobial agents and chemotherapy2024

Pharmacokinetic-pharmacodynamic modeling of tuberculosis time to positivity and colony-forming unit to assess the response to dose-ranging linezolid.

Segolene Simeon, Maria Garcia-Cremades, Rada Savic, Belén P Solans

Registry-linked trialAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02279875 (A Phase 2 Dose-ranging Trial to Evaluate the Bactericidal Activity, Safety, Tolerability and Pharmacokinetics of Linezolid in Adult Subjects With Newly Diagnosed Drug-Sensitive, Smear-Positive Pulmonary Tuberculosis.), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02279875 phase2completednot on this map

A Phase 2 Dose-ranging Trial to Evaluate the Bactericidal Activity, Safety, Tolerability and Pharmacokinetics of Linezolid in Adult Subjects With Newly Diagnosed Drug-Sensitive, Smear-Positive Pulmonary Tuberculosis.

TypeinterventionalSponsorGlobal Alliance for TB Drug DevelopmentRan2014 to 2017Enrolled113ConditionsPulmonary TuberculosisArmsLinezolid, HRZE (isoniazid rifampicin,pyrazinamide,ethambutol)
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Insights into the Role of Rifampicin Exposure and Clinical Baseline Covariates on the Response to Pulmonary Tuberculosis Treatment.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Article
  2. Article
  3. Article
  4. Anti-TB Drugs for Drug-Sensitive and Drug-ResistantCurrent issues in molecular biology · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Segolene SimeonDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine, San Francisco, California, USA.ORCID 0000-0002-6068-7786
Maria Garcia-CremadesDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine, San Francisco, California, USA.
Rada SavicDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine, San Francisco, California, USA.ORCID 0000-0003-3143-5579
Belén P SolansDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco Schools of Pharmacy and Medicine, San Francisco, California, USA.ORCID 0000-0003-4621-5480

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

According to the World Health Organization, the number of tuberculosis (TB) infections and the drug-resistant burden worldwide increased by 4.5% and 3.0%, respectively, between 2020 and 2021. Disease severity and complexity drive the interest for undertaking new clinical trials to provide efficient treatment to limit spread and drug resistance. TB Alliance conducted a phase 2 study in 106 patients to guide linezolid (LZD) dose selection using early bactericidal activity over 14 days of treatment. LZD is highly efficient for drug-resistant TB treatment, but treatment monitoring is required since serious adverse events can occur. The objective of this study was to develop a pharmacokinetic-pharmacodynamic (PKPD) model to analyze the dose-response relationship between linezolid exposure and efficacy biomarkers. Using time to positivity (TTP) and colony-forming unit (CFU) count data, we developed a PKPD model in six dosing regimens, differing on LZD dosing intensity. A one-compartment model with five transit absorption compartments and non-linear auto-inhibition elimination described best LZD pharmacokinetic characteristics. TTP and CFU logarithmic scaled [log(CFU)] showed a bactericidal activity of LZD against CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT02279875.

Indexed as

Antitubercular AgentsLinezolidMycobacterium tuberculosisAdultColony Count, MicrobialDose-Response Relationship, DrugFemaleHumansMaleMicrobial Sensitivity TestsMiddle AgedTuberculosisTuberculosis, Multidrug-ResistantAntitubercular AgentsLinezolidcolony-forming unitearly bactericidal activitytime-to-positivitytuberculosis

Identifiers

PMID39016594
PMCPMC11323931

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.